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Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 287-290

LEOPARD syndrome with late onset lentigines: A rarity


Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Dr. Kaliaperumal Karthikeyan
Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthalkuppam, Madagadipet, Puducherry - 605 107
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_4_17

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How to cite this article:
Nagakeerthana S, Madhavi S, Karthikeyan K. LEOPARD syndrome with late onset lentigines: A rarity. Indian J Paediatr Dermatol 2018;19:287-90

How to cite this URL:
Nagakeerthana S, Madhavi S, Karthikeyan K. LEOPARD syndrome with late onset lentigines: A rarity. Indian J Paediatr Dermatol [serial online] 2018 [cited 2019 Dec 10];19:287-90. Available from: http://www.ijpd.in/text.asp?2018/19/3/287/206077



Sir,

 LEOPARD syndrome More Details (LS) is a rare hereditary disorder characterized by skin, facial, and cardiac anomalies. LEOPARD is an acronym for the major feature of this disorder, including multiple lentigines, electrocardiogram (ECG) abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness.[1] This neuro-cardio-facial-cutaneous genetic syndrome is mostly an autosomal-dominant disorder, caused by germline missense mutation in PTPN11 located on chromosome 12q22.[2]

A 14-year-old female presented to us with complaints of multiple, tiny, dark spots over her face [Figure 1]. The spots appeared on the face at the age of 13 and gradually increased in number. The spots were asymptomatic and not associated with photosensitivity. She was born of a second degree consanguineous marriage and had a history of seizures. She denied any history of syncopal attacks, dyspnea, and cyanosis. There was no history of difficulty in hearing, abnormalities of genitalia or skeletal abnormalities.
Figure 1: Face shows prominent abnormality such as lentiginosis, hypertelorism, and broad nose

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On general examination, she was undernourished, and her height was 134 cm (below 5th percentile for her age). She had hypertelorism with a broad nasal root and ears appeared low set with everted helix [Figure 1] and [Figure 2]. The patient also had speech difficulty. Her cardiac examination, ECG, and echocardiography were normal. Pure tone audiometry showed normal hearing limits. Her routine blood and urine examination were normal. Ultrasound study showed normal genitourinary system. Her intelligence was assessed with Binet–Kamat test; it showed her mental age as 6 years, IQ was 42 and inadequate in basic cognitive function.
Figure 2: Low set ears

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On cutaneous examination, multiple lentigines were seen over bilateral malar region, nose, lips, and chin. Her external genitalia was normal. The diagnosis was based on the criteria proposed by Voron et al. Our patient has the major criteria (lentiginosis) along with three minor criteria (craniofacial dysmorphism: Hypertelorism, broad nasal root, low-set ears; skeletal abnormalities: Short stature and neurological abnormalities: Mental retardation and seizures).

Lentigines are flat-pigmented macules on the skin and mucosa. They are characterized by their small size of <0.5 cm, irregular borders, and discrete lesions of brown and black shades.[3] On histological examination of lentigines, a horizontal increase in the number of melanocytes at the dermoepidermal junction, increased number of melanin in the epidermis will be present. This feature is distinct from the histological appearance of freckles. Freckles contain a normal number of melanocytes and are pigmented due to increased melanin in basal keratinocytes.[3] While lentigines may occur on all parts of the body, freckles are found on sun-exposed parts of the body and also darkens with sun exposure. Specific sites of pigmentation, such as the labia majora, palms and soles, conjunctivae, and vermillion border of the lips, are characteristic locations for lentigines.[4] In our patient, lentigines were present over the lips as well as centrofacial region. Lentigines can also occur as a part of the syndrome [Table 1], one such syndrome is LS.[4],[8]
Table 1: Syndromes associated with lentigines

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LS is a rare condition. About 200 patients with this syndrome have been reported worldwide.[2] After Noonan syndrome, it is the second most common disorder within the group “neuro-cardio-facial-cutaneous syndromes.” This disease was also known as multiple lentigines syndrome, cardio-cutaneous syndrome,  Moynahan syndrome More Details, lentiginosis profuse, and progressive cardiomyopathic lentiginosis.[2]

Patients with LS usually do not present with all the clinical features associated with the disorder. At times, several features are not present until late in life and do not clinically manifest until puberty. Lentigines are observed in almost all the patients with LS, followed by electrocardiographic abnormalities (80%), skeletal abnormalities (60%), hypertelorism (50%), short stature (42%), mental retardation (35%), abnormal male genitalia (29%), and deafness (27%).[5] Musculoskeletal involvement leading to thorax anomalies such as broad chest, pectus carinatum, or excavatum is found in up to 75% of the newborns.[6] The lentigines may be congenital, although more frequently it appears by the age of 4–5 years and increase throughout puberty.[2] In our patient, the onset was after puberty. Late onset lentigines in LS have not been described in the literature to the best of our knowledge.

A diagnosis of LS may be established exclusively on the basis of Voron's clinical criteria [Table 2], tabulated by Ghosh et al.[2] In addition to the multiple lentigines, the presence of two out of the listed anomalies is sufficient for diagnosis. If no lentigo is present, findings from at least three categories must be present and a first-degree relative of the patient must have lentigines.[4] Further, lentigines which give a clue to diagnosis may occur at any age as in our case. In our patient, facial abnormality was more predominant, which included lentiginosis, hypertelorism, and low-set ears. Some individuals may show mild mental retardation, speech disorders and/or additional physical anomalies as seen in our patient. A study by Sarkozy et al. revealed that mutations were also found in patients who did not fulfill Voron's criteria.[7] As the patients do not present with all the clinical features which are associated with the disorder, there are high chances that LS is underdiagnosed or misdiagnosed. Therefore, when a patient with lentigines presents to us, the criteria should be kept in mind, and LS should be ruled out along with other familial lentiginosis syndromes. In young patients with only partial phenotypes, molecular testing can be done to confirm the diagnosis. Further studies and reports are required to find whether there is any relationship between late onset of lentigines and other manifestations in LS.
Table 2: Clinical manifestations of LEOPARD syndrome

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sarkozy A, Digilio MC, Dallapiccola B. Leopard syndrome. Orphanet J Rare Dis 2008;3:1-8.  Back to cited text no. 1
    
2.
Ghosh S, Chaudhuri S, Jain VK. Leopard syndrome with Wolff-Parkinson-White syndrome on electrocardiography. Indian J Dermatol Venereol Leprol 2013;79:821-4.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
James MG, Arthur RR, Arthur JS. Benign neoplasias and hyperplasias of melanocytes. In: Fitzpatrick TB, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw-Hill; 2008. p. 1099-121.  Back to cited text no. 3
    
4.
Lodish MB, Stratakis CA. The differential diagnosis of familial lentiginosis syndromes. Fam Cancer 2011;10:481-90.  Back to cited text no. 4
[PUBMED]    
5.
Porciello R, Divona L, Strano S, Carbone A, Calvieri C, Giustini S. Leopard syndrome. Dermatol Online J 2008;14:7.  Back to cited text no. 5
    
6.
Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R, et al. Leopard syndrome: Clinical diagnosis in the first year of life. Am J Med Genet A 2006;140:740-6.  Back to cited text no. 6
[PUBMED]    
7.
Sarkozy A, Conti E, Digilio MC, Marino B, Morini E, Pacileo G, et al. Clinical and molecular analysis of 30 patients with multiple lentigines Leopard syndrome. J Med Genet 2004;41:e68.  Back to cited text no. 7
[PUBMED]    
8.
Scully C. Dermatoses of oral cavity and lips. In: Griffiths CE, Barker J, Bleiker T, Chalmers R, Creamer D, editors. Rook's Textbook of Dermatology. 9th ed. Chichester: Wiley-Blackwell; 2016. p. 110.11-110.13.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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